Syntheses of 1,3,4-Thia(oxa)diazole-substituted Pyrazole Derivatives and Their Fungicidal Activities

A series of 1,3,4-oxadiazole or 1,3,4-thiadiazole-substituted pyrazole derivatives were synthesized from 4-pyrazole formhydrazide; their biological activities were studied. The structures of all the new compounds were confirmed by means of spectroscopic methods and microanalyses. The preliminary bioassay results indicate that some compounds of them have a good fungicidal activity against Phoma asparagi and Physalospora piricola Nose.

Synthesis and Crystal Structure of 3-{[(1E)1-(2-Hydroxyphenyl) methylidene]amino}-4-cyanopyrazole

The title Schiff base compound （C11H8N4O）, a derivative of pyrazole, has been synthesized by the reaction of salicylaldehyde and 3-amino-4-cyanopyrazole in absolute ethanol and characterized by elemental analyses, IR, ^1H NMR and X-ray single-crystal diffraction. The crystal belongs to the monoclinic system, space group P21/n, with a = 7.5594（7）, b = 18.3342（19）, c = 22.461（2） A^°, β = 98.419（2）°, V = 3079.5（5） A^°3, Mr = 212.21, Z = 12, F（000） = 1320, Dc = 1.373 g/cm^3, T = 298（2） K, 2 = 0.71073 A^°, the final R = 0.0571 and wR = 0.0493. A total of 5412 unique reflections were collected, of which 1612 with I 〉 2σ（I） were observed. The molecular structure adopts a trans configuration about the C=N double bond. The preliminary biological tests show that the compound has high antibacterial activities.

Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 mu mol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Novel pyrazole fused heterocyclic ligands:Synthesis,characterization,DNA binding/cleavage activity and anti-BVDV activity

A series of novel pyrazole fused heterocyclic derivatives were synthesized via a two-step procedure or a one-pot two step method, and their catalytic DNA cleavage abilities and anti-BVDV activities were also evaluated. The results obtained indicated that compounds 3b-3c could catalyze the cleavage of supercoiled DNA （pUC 19 plasmid DNA） to nicked DNA under physiological conditions with high yields via a hydrolytic mechanism. The studies on anti-viral activities against bovine viral diarrhea virus （BVDV） demonstrated that some of the pyrazole derivatives showed pronounced anti-BVDV activity with interesting ECso values and no significant cytotoxicity. Among them, compound 31 showed the highest antiviral activity （ECso = 0.12 μmol/L） and was 10 fold more than that of the positive control ribavirin （ECso = 1.3 μmol/L）, which provided a potential candidate for the development of anti-BVDV agents.

Synthesis and biological activity of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives

A series of novel N-（3-furan-2-yl-l-phenyl-lH-pyrazol-5-yl） amides derivatives were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR and HRMS. All title compounds were evaluated for their herbicidal and antifungal activities. Preliminary bioassay results indicated that the title compounds showed good to moderate herbicidal activity at 1000 mg/L. Compound 6q presented the best activity against Digitaria sanguinalis （L） Scop., Amaranthus retroflexus L. and Arabidopsis thaliana with an inhibition degree of five. Compound 6d also showed an inhibition degree of five against D. sanguinalis. In addition, at 50 mg/L, most compounds exhibited good in vitro antifungal activity against Sclerotinia sclerotiorum, with compound 6c showing over 90% antifungal activity against S. sclerotiorum and Pellicularia sasakii.